Study Title:

The Methylation, Neurotransmitter, and Antioxidant Connections Between Folate and Depression

Study Abstract

Depression is common – one-fourth of the U.S. population will
have a depressive episode sometime in life. Folate deficiency is
also relatively common in depressed people, with approximately
one-third of depressed individuals having an outright deficiency.
Folate is a water-soluble B-vitamin necessary for the proper
biosynthesis of the monoamine neurotransmitters serotonin,
epinephrine, and dopamine. The active metabolite of folate,
5-methyltetrahydrofolate (5-MTHF, L-methylfolate), participates
in re-methylation of the amino acid metabolite homocysteine,
creating methionine. S-adenosylmethionine (SAMe), the
downstream metabolite of methionine, is involved in numerous
biochemical methyl donation reactions, including reactions
forming monoamine neurotransmitters. Without the participation
of 5-MTHF in this process, SAMe and neurotransmitter levels
decrease in the cerebrospinal fluid, contributing to the disease
process of depression. SAMe supplementation was shown to
improve depressive symptoms. 5-MTHF also appears to stabilize,
enhance production of, or possibly act as a substitute for,
tetrahydrobiopterin (BH4), an essential cofactor in monoamine
neurotransmitter biosynthesis. There are few intervention
studies of folic acid or 5-MTHF as a stand-alone treatment for
depression related to folate deficiency; however, the studies
that have been conducted are promising. Depressed individuals
with low serum folate also tend to not respond well to selective
serotonin reuptake inhibitor (SSRI) antidepressant drugs.
Correcting the insufficiency by dosing folate along with the
SSRI results in a significantly better antidepressant response

Study Information

The Methylation, Neurotransmitter, and Antioxidant Connections Between Folate and Depression
Alternative Medicine Review
2008 November

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